The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice
<i>MCPH1</i> is the first gene identified to be responsible for the human autosomal recessive disorder primary microcephaly (MCPH). Mutations in the N-terminal and central domains of MCPH1 are strongly associated with microcephaly in human patients. A recent study showed that the central...
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MDPI AG
2022-08-01
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| author | Yaru Wang Wen Zong Wenli Sun Chengyan Chen Zhao-Qi Wang Tangliang Li |
| author_facet | Yaru Wang Wen Zong Wenli Sun Chengyan Chen Zhao-Qi Wang Tangliang Li |
| author_sort | Yaru Wang |
| collection | DOAJ |
| description | <i>MCPH1</i> is the first gene identified to be responsible for the human autosomal recessive disorder primary microcephaly (MCPH). Mutations in the N-terminal and central domains of MCPH1 are strongly associated with microcephaly in human patients. A recent study showed that the central domain of MCPH1, which is mainly encoded by exon 8, interacts with E3 ligase βTrCP2 and regulates the G2/M transition of the cell cycle. In order to investigate the biological functions of MCPH1’s central domain, we constructed a mouse model that lacked the central domain of MCPH1 by deleting its exon 8 (designated as <i>Mcph1</i>-Δe8). <i>Mcph1</i>-Δe8 mice exhibited a reduced brain size and thinner cortex, likely caused by a compromised self-renewal capacity and premature differentiation of <i>Mcph1</i>-Δe8 neuroprogenitors during corticogenesis. Furthermore, <i>Mcph1</i>-Δe8 mice were sterile because of a loss of germ cells in the testis and ovary. The embryonic fibroblasts of <i>Mcph1</i>-Δe8 mice exhibited premature chromosome condensation (PCC). All of these findings indicate that <i>Mcph1</i>-Δe8 mice are reminiscent of MCPH1 complete knockout mice and <i>Mcph1</i>-ΔBR1 mice. Our study demonstrates that the central domain of MCPH1 represses microcephaly, and is essential for gonad development in mammals. |
| first_indexed | 2024-03-10T01:57:18Z |
| format | Article |
| id | doaj.art-db47d9d54b484d1aa374fa09d5a51b09 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:57:18Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-db47d9d54b484d1aa374fa09d5a51b092023-11-23T12:55:45ZengMDPI AGCells2073-44092022-08-011117271510.3390/cells11172715The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in MiceYaru Wang0Wen Zong1Wenli Sun2Chengyan Chen3Zhao-Qi Wang4Tangliang Li5State Key Laboratory of Microbial Technology, Shandong University, Qingdao 250100, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao 250100, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao 250100, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao 250100, ChinaLeibniz Institute on Aging—Fritz Lipmann Institute (FLI), 07745 Jena, GermanyState Key Laboratory of Microbial Technology, Shandong University, Qingdao 250100, China<i>MCPH1</i> is the first gene identified to be responsible for the human autosomal recessive disorder primary microcephaly (MCPH). Mutations in the N-terminal and central domains of MCPH1 are strongly associated with microcephaly in human patients. A recent study showed that the central domain of MCPH1, which is mainly encoded by exon 8, interacts with E3 ligase βTrCP2 and regulates the G2/M transition of the cell cycle. In order to investigate the biological functions of MCPH1’s central domain, we constructed a mouse model that lacked the central domain of MCPH1 by deleting its exon 8 (designated as <i>Mcph1</i>-Δe8). <i>Mcph1</i>-Δe8 mice exhibited a reduced brain size and thinner cortex, likely caused by a compromised self-renewal capacity and premature differentiation of <i>Mcph1</i>-Δe8 neuroprogenitors during corticogenesis. Furthermore, <i>Mcph1</i>-Δe8 mice were sterile because of a loss of germ cells in the testis and ovary. The embryonic fibroblasts of <i>Mcph1</i>-Δe8 mice exhibited premature chromosome condensation (PCC). All of these findings indicate that <i>Mcph1</i>-Δe8 mice are reminiscent of MCPH1 complete knockout mice and <i>Mcph1</i>-ΔBR1 mice. Our study demonstrates that the central domain of MCPH1 represses microcephaly, and is essential for gonad development in mammals.https://www.mdpi.com/2073-4409/11/17/2715microcephalyMCPH1central domainbrain developmentgonad development |
| spellingShingle | Yaru Wang Wen Zong Wenli Sun Chengyan Chen Zhao-Qi Wang Tangliang Li The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice Cells microcephaly MCPH1 central domain brain development gonad development |
| title | The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice |
| title_full | The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice |
| title_fullStr | The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice |
| title_full_unstemmed | The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice |
| title_short | The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice |
| title_sort | central domain of mcph1 controls development of the cerebral cortex and gonads in mice |
| topic | microcephaly MCPH1 central domain brain development gonad development |
| url | https://www.mdpi.com/2073-4409/11/17/2715 |
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